Studies of immunity indicate the emergence of two types of adaptive immune systems (AISs) in vertebrates. Humans generate a vast repertoire of Ig-domain-based T- and B-cell antigen receptors primarily by the assembly of Ig V-(D)-J gene segments and somatic hypermutation. Lampreys and hagfish have alternative AISs that are based on variable lymphocyte receptors (VLRs), the diversity of which is generated from leucine-rich repeat (LRR) cassettes. The combinatorial VLR assembly can generate a vast repertoire of receptors comparable in diversity to human immunoglobulins. See Han et al. Antigen recognition by variable lymphocyte receptors, Science, 2008 321:1834-183; Hirano et al., The evolution of adaptive immunity in vertebrates, Adv Immunol, 2011, 109:125-57; WO 2013/078425; US 2011/0230374; WO 2010/065407; and WO 2008/016854. Guo et al. report the adaptive immune system in lampreys. Nature, 2009, 459(7248):796-80. Tasumi et al. report high-affinity lamprey VLRA and VLRB monoclonal antibodies. Proc Natl Acad Sci USA, 2009, 106(31):12891-6. Nakahara et al. report chronic lymphocytic leukemia monitoring with a lamprey idiotope-specific antibody. Cancer Immunol Res, 2013, 1(4):223-228.
Binz et al., report engineering binding proteins from non-immunoglobulin domains. Nat Biotechnol., 2005, 23(10):1257-68.
Lee et al. report a binding scaffold based on variable lymphocyte receptors of jawless vertebrates by module engineering. Proc Natl Acad Sci USA, 2012, 109(9):3299-304.
References cited herein are not an admission of prior art.